Vaccination of hiv infected persons following highly active antiretrovial therapy

Abstract

The present invention provides a method of permitting cessation of antiviral therapy on HIV-infected subjects without virus rebound or with at least a delayed virus rebound or a decreased post rebound set-point. The method comprises the re-induction of HIV-specific immune responses using a vaccination strategy to induce both humoral and cell-mediated immunity. The present invention achieves an immunological control of persistent infectious virus after discontinuation of antiviral therapy. The vaccine strategy according to the invention is both safe and immunogenic in the subject HIV-infected patient population.

We claim:  
     
         1 . A method of treating HIV-infected patients, the method comprising: 
 a) subjecting the patient to antiviral therapy;    b) administering to the subject one or a plurality of nucleic acid-based vaccines that enter the patient's cells and intracellularly produce one or a plurality of HIV-specific immunogens for presentation on the cell's MHC class I and MHC class II molecules in an amount sufficient to stimulate an HIV-specific CD8+ and CD4+ responses;    c) ceasing said antiviral therapy.    
     
     
         2 . The method according to  claim 1 , wherein the antiviral therapy is HAART.  
     
     
         3 . The method according to  claim 2  wherein before administering the nucleic acid-based vaccine or vaccines, the patient has a viral load of less than 10,000 viral copies per ml of plasma and a CD4+ T-cell count of above 300 cells/ml before administration of vaccine.  
     
     
         4 . The method according to  claim 2  wherein before administering the nucleic acid-based vaccine or vaccines, the patient has a viral load of less than 5,000 viral copies per ml of plasma CD4+ T-cell count of above 300 cells/ml before administration of vaccine.  
     
     
         5 . The method according to  claim 2  wherein before administering the nucleic acid-based vaccine or vaccines, the patient has a viral load of less than 1,000 viral copies per ml of plasma CD4+ T-cell count of above 300 cells/ml before administration of vaccine.  
     
     
         6 . The method according to  claim 2  wherein before administering the nucleic acid-based vaccine or vaccines, the patient has a viral load of less than 10,000 viral copies per ml of plasma CD4+ T-cell count of above 500 cells/ml before administration of vaccine.  
     
     
         7 . The method according to  claim 2  wherein before administering the nucleic acid-based vaccine or vaccines, the patient has a viral load of less than 5,000 viral copies per ml of plasma CD4+ T-cell count of above 500 cells/ml before administration of vaccine.  
     
     
         8 . The method according to  claim 2  wherein before administering the nucleic acid-based vaccine or vaccines, the patient has a viral load of less than 1,000 viral copies per ml of plasma CD4+ T-cell count of above 500 cells/ml before administration of vaccine.  
     
     
         9 . The method according to  claim 2  wherein the patient exhibits CD4+ and/or CD8+ T-cell responses to HIV.  
     
     
         10 . The method according to  claim 2  wherein the patient exhibits CD4+ and CD8+ T-cell responses to envelope epitopes.  
     
     
         11 . The method according to  claim 2  wherein the patient exhibits CD4+and CD8+ T cell responses to Gag epitopes.  
     
     
         12 . The method according to  claim 2  wherein the patient has lost his CD4+ and/or CD8+ T cell responses to HIV antigens.  
     
     
         13 . The method according to  claim 2  wherein the patient has lost his CD4+ and CD8+ T cell responses to envelope and Gag HIV epitopes.  
     
     
         14 . The method according to  claim 2  wherein the HIV specific immunogen is gp120.  
     
     
         15 . The method according to  claim 2  wherein the HIV-specific immunogen is Gag.  
     
     
         16 . The method according to  claim 2  wherein the nucleic acid-based vaccine comprises one or a plurality of naked DNAs encoding one or a plurality of HIV-specific immunogens.  
     
     
         17 . The method according to  claim 2  wherein the nucleic acid-based vaccine comprises one or a plurality of DNA vectors encoding one or a plurality of HIV-specific immunogens.  
     
     
         18 . The method according to  claim 17  wherein the DNA vector is a recombinant virus.  
     
     
         19 . The method according to  claim 17  wherein the DNA vector is a recombinant attenuated virus.  
     
     
         20 . The method according to  claim 18  wherein the recombinant attenuated virus is selected from the group consisting of adenoviruses, adeno-associated viruses, human influenza viruses, herpes simplex virus (HSV), coksackie viruses, Vesicular stomatitis viruses (VSV), and alphaviruses.  
     
     
         21 . The method according to  claim 18  wherein the recombinant attenuated virus is a poxvirus.  
     
     
         22 . The method according to  claim 21  wherein the recombinant attenuated virus is selected from the group consisting of vaccinia, avipox, fowlpox, and canarypox.  
     
     
         23 . The method according to  claim 22  wherein the recombinant attenuated virus is NYVAC or ALVAC.  
     
     
         24 . The method according to  claim 18  wherein the recombinant attenuated virus is MVA.  
     
     
         25 . The method according to  claim 18  wherein the HIV-specific immunogen is a structural protein.  
     
     
         26 . The method according to  claim 25  wherein the HIV-specific immunogen is a structural protein selected from the group consisting of gp 160, gp 120, gp 41, and Gag.  
     
     
         27 . The method according to  claim 18  wherein the HIV-specific immunogen is a non-structural protein.  
     
     
         28 . The method according to  claim 27  wherein the HIV-specific immunogen is a non-structural protein encoded by a gene selected from the group consisting of rev, tat, nef, vif, and vpr.  
     
     
         29 . The method according to  claim 18  wherein the HIV-specific Immunogen is selected from the group consisting of HIV-1 Gag, gp120, NefCTL, PoICTL epitopes.  
     
     
         30 . The method according to  claim 18  wherein the HIV-specific immunogen presents at least one epitope selected from the group consisting of ELDKWA, LDKW, Nef1, Nef2, the V3 loop, Pol1, Pol2 and Pol3.  
     
     
         31 . The method according to  claim 18  wherein the HIV-specific immunogen presents at least one epitope of a peptide selected from the group consisting of gp 160, gp 120, gp 41, Gag, and at least one protein encoded by the rev, tat, nef, vif, or vpr gene.  
     
     
         32 . The method according to  claim 2  wherein the nucleic acid-based vaccine comprises a construct selected from the group consisting of vCP1452, vCP1433, vCPI25, vCP205, and VCP300.  
     
     
         33 . The method according to any one of claims  18 ,  21 ,  23 ,  26 ,  28 , and  31  wherein the vaccine is administered. simultaneously or sequentially, with a soluble HIV antigen.  
     
     
         34 . The method according to  claim 33 , wherein the soluble HIV antigen is gp160.  
     
     
         35 . The method according to  claim 33 , wherein the soluble HIV antigen is recombinant gp 160MN/LAI.